An enhanced recovery after surgery pathway for cesarean delivery decreases hospital stay and cost.

BACKGROUND: Enhanced recovery after surgery pathways provide a multidisciplinary, evidence-based approach to the care of surgical patients. They have been shown to decrease postoperative length of stay and cost in several surgical subspecialties, including gynecology, but have not been well-studied in obstetric patients who undergo cesarean delivery. OBJECTIVE: We sought to determine whether the implementation of an enhanced recovery after surgery pathway for cesarean delivery would decrease postoperative length of stay and postoperative direct cost compared with historic controls. STUDY DESIGN: We conducted a retrospective cohort study that compared postoperative length of stay and postoperative direct cost among women on the enhanced recovery after surgery cesarean delivery pathway in the first year of implementation (April 1, 2017, to March 31, 2018; n=531) compared with historic controls (March 1, 2016, to February 28, 2017; n=661). Literature review informed the development of a prototype enhanced recovery after surgery pathway for cesarean delivery based on best practices from previous enhanced recovery after surgery experience in obstetrics (if available) or from other surgical disciplines if there were no available data for obstetrics. When there was not relevant published evidence from obstetrics, the taskforce used clinical experience and expert opinion to develop the pathway. The enhanced recovery after surgery cesarean delivery pathway included preadmission patient education and preoperative, intrapartum, and postoperative elements. Some components reflected standard obstetric care, and others were specific to the enhanced recovery after surgery pathway. Women with pregestational diabetes mellitus who were receiving insulin therapy before pregnancy, women with preeclampsia with severe features, women with complex pain needs, and women with surgical complications were excluded from baseline and implementation groups. Enhanced recovery after surgery cesarean delivery pathway participation was determined by order set usage. Analysis was stratified for women who underwent planned (no labor; n=530) and unplanned (labor; n=662) cesarean delivery. Demographic and clinical characteristics, postoperative length of stay, postoperative direct cost, and readmission rates for the baseline and implementation groups were compared with the use of chi-square and t-tests. RESULTS: During the first year of implementation, 531 of 640 eligible women (83%) were included in the enhanced recovery after surgery cesarean delivery pathway. Body mass index was marginally higher in the baseline group for unplanned cesarean delivery (32.5±7.1 vs 31.4±6.7 kg/m2; P=.04). Otherwise there were no significant differences in demographic or maternal clinical characteristics between baseline or implementation groups overall or for planned or unplanned cesarean delivery. Compared with baseline, implementation of the enhanced recovery after surgery cesarean delivery pathway resulted in a significant decrease in postoperative length of stay by 7.8% or 4.86 hours overall (P<.001) and for both planned (P=.001) and unplanned (P=.002) cesarean delivery. Total postoperative direct costs decreased by 8.4% or $642.85 per patient overall (P<.001) and for both planned (P<.001) and unplanned (P<.001) cesarean delivery. There were no significant differences in readmission rates. CONCLUSION: Implementation of an enhanced recovery after surgery pathway for women who had planned or unplanned cesarean delivery was associated with significantly decreased postoperative length of stay and significant direct cost-savings per patient, without an increase in hospital readmissions. Given that cesarean delivery is 1 of the most common surgical procedures performed in the United States, positively impacting postoperative length of stay and direct cost for women who undergo cesarean delivery could have significant healthcare cost-savings.

Human immunodeficiency viruses appear compartmentalized to the female genital tract in cross-sectional analyses but genital lineages do not persist over time.

BACKGROUND: Whether unique human immunodeficiency type 1 (HIV) genotypes occur in the genital tract is important for vaccine development and management of drug resistant viruses. Multiple cross-sectional studies suggest HIV is compartmentalized within the female genital tract. We hypothesize that bursts of HIV replication and/or proliferation of infected cells captured in cross-sectional analyses drive compartmentalization but over time genital-specific viral lineages do not form; rather viruses mix between genital tract and blood. METHODS: Eight women with ongoing HIV replication were studied during a period of 1.5 to 4.5 years. Multiple viral sequences were derived by single-genome amplification of the HIV C2-V5 region of env from genital secretions and blood plasma. Maximum likelihood phylogenies were evaluated for compartmentalization using 4 statistical tests. RESULTS: In cross-sectional analyses compartmentalization of genital from blood viruses was detected in three of eight women by all tests; this was associated with tissue specific clades containing multiple monotypic sequences. In longitudinal analysis, the tissues-specific clades did not persist to form viral lineages. Rather, across women, HIV lineages were comprised of both genital tract and blood sequences. CONCLUSIONS: The observation of genital-specific HIV clades only in cross-sectional analysis and an absence of genital-specific lineages in longitudinal analyses suggest a dynamic interchange of HIV variants between the female genital tract and blood.

Inadequate prenatal care and risk of preterm delivery among adolescents: a retrospective study over 10 years.

OBJECTIVE: The aim of this study was to determine whether inadequate prenatal care is associated with increased risk of preterm birth among adolescents. STUDY DESIGN: We selected a random sample of women under age 20 years with singleton pregnancies delivering in Washington State between 1995 and 2006. Multivariate logistic regression was used to assess the association between prenatal care adequacy (percent of expected visits attended, adjusted for gestational age) and preterm birth. RESULTS: Of 30,000 subjects, 27,107 (90%) had complete data. Women without prenatal care had more than 7-fold higher risk of preterm birth (n = 84 [24.1%]; adjusted odds ratio [aOR], 7.4), compared with those attending 75-100% of recommended visits (n = 346 [3.9%]). Women with less than 25%, 25-49%, or 50-74% of expected prenatal visits were at significantly increased risk of preterm birth; risk decreased linearly as prenatal care increased (n = 60 [9.5%], 132 (5.9%], 288 [5%]; and aOR, 2.5, 1.5, and 1.3, respectively). CONCLUSION: Inadequate prenatal care is strongly associated with preterm birth among adolescents.

Agricultural-related chemical exposures, season of conception, and risk of gastroschisis in Washington State.

OBJECTIVE: We sought to determine if periconceptional exposure to agrichemicals was associated with the development of gastroschisis. STUDY DESIGN: We conducted a retrospective, case-controlled study using Washington State Birth Certificate and US Geological Survey databases. Cases included all live-born singleton infants with gastroschisis. Distance between a woman's residence and site of elevated exposure to agrichemicals was calculated. Multivariate regression was used to estimate the association between surface water concentrations of agrichemicals and the risk of gastroschisis. RESULTS: Eight hundred five cases and 3616 control subjects were identified. Gastroschisis occurred more frequently among those who resided <25 km from a site of high atrazine concentration (odds ratio, 1.6). Risk was related inversely to the distance between the maternal residence and the closest toxic atrazine site. In multivariate analysis, nulliparity, tobacco use, and spring conception remained significant predictive factors for gastroschisis. CONCLUSION: Maternal exposure to surface water atrazine is associated with fetal gastroschisis, particularly in spring conceptions.

Comparison of oral and vaginal metronidazole for treatment of bacterial vaginosis in pregnancy: impact on fastidious bacteria.

BACKGROUND: Bacterial vaginosis (BV) is a common condition that is associated with preterm birth and acquisition of complex communities of vaginal bacteria that include several fastidious species. Treatment of BV in pregnancy has mixed effects on the risk of preterm delivery, which some hypothesize is due to variable antibiotic efficacy for the fastidious bacteria. Both oral and intravaginal metronidazole can be used to treat bacterial vaginosis in pregnancy, but little is known about the impact of different routes of antibiotic administration on concentrations of fastidious vaginal bacteria. METHODS: This was a sub-study of a larger randomized trial of oral versus vaginal metronidazole for treatment of BV in pregnancy. Fifty-three women were evaluated, including 30 women who received oral metronidazole and 23 who received intravaginal metronidazole. Bacterial taxon-specific quantitative PCR assays were used to measure concentrations of bacterial vaginosis associated bacterium (BVAB) 1, 2, and 3, Gardnerella vaginalis, Atopobium species, Leptotrichia/Sneathia species, Megasphaera species, and Lactobacillus crispatus before and after antibiotic treatment. RESULTS: Concentrations of Leptotrichia and Sneathia spp. and the fastidious Clostridia-like bacterium designated BVAB1 decreased significantly with oral (p = .002, p = .02) but not vaginal therapy (p = .141, p = .126). The fastidious bacterium BVAB3 did not significantly decrease with either treatment. Concentrations of Atopobium spp., reportedly resistant to metronidazole in vitro, dropped significantly with oral (p = .002) and vaginal (p = .001) treatment. There was no significant difference in the magnitude of change in bacterial concentrations between oral and vaginal treatment arms for any of the bacterial species. Lactobacillus crispatus concentrations did not change. CONCLUSION: Both oral and vaginal metronidazole therapy in pregnant women result in a significant decrease in concentrations of most BV-associated anaerobic bacteria, with the exception that Leptotrichia, Sneathia and BVAB1 do not significantly decrease with vaginal metronidazole therapy. These data suggest that the route of antibiotic administration has a minor impact on bacterial eradication in pregnant women with BV. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, number NCT00153517.

Partner- and partnership-related risk factors for preterm birth among low-income women in Lima, Peru.

A woman's partner and the characteristics of their partnership can play an important role in the health of her pregnancy. Yet, with the notable exception of intimate partner violence, there has been little previous research addressing the associations between partner- or partnership-related factors and birth outcomes. This analysis tested the hypothesis that risk factors related specifically to partner or partnership characteristics increased the risk for preterm birth. Between 2003 and 2005, a total of 580 preterm cases (20-36 weeks gestational age at delivery) and 633 term controls (> or =37 weeks) were selected from women delivering at an obstetric hospital in Lima, Peru. Each woman completed a confidential, structured interview and provided biological specimens within 48 h after delivery. Multivariable logistic regression was used to assess associations between partner and partnership characteristics and preterm birth. After adjustment for behavioral, demographic, and obstetric risk factors, ever having had a partner with a history of drug use (aOR = 1.91, 95% CI 1.22-2.99), ever having had anal sex (aOR = 1.40, 95% CI 1.07-1.84), having a current partner with a history of visiting prostitutes (aOR = 1.69, 95% CI 1.22-2.33), and perceiving one's current partner as a "womanizer" (aOR = 1.34, 95% CI 1.02-1.77) were significantly associated with an elevated risk of preterm birth when tested in separate models. These four factors were then used to create a composite partnership risk score, which showed an increasing dose-response relationship with preterm birth risk (per additional partner risk factor: aOR = 1.31, 95% CI 1.16-1.49). These results highlight the importance of considering a broader set of risk factors for preterm birth, specifically those related to a woman's partner and partnership characteristics. Further research could clarify the specific mechanisms through which these partner and partnership characteristics may increase the risk of preterm birth.

Antiretroviral pharmacokinetic profile: a review of sex differences.

BACKGROUND: Emerging evidence suggests that female sex may be associated with increased risk of developing antiretroviral toxicities. Although the mechanisms of sex-related antiretroviral pharmacodynamic differences remain poorly understood and may be multifactorial, they appear to be mediated through a common pathway of pharmacokinetic variability between the sexes. OBJECTIVE: This article reviews sex differences in the pharmacokinetics of the major classes of antiretroviral drugs currently approved for HIV treatment by the US Food and Drug Administration, identifies knowledge gaps, and provides recommendations for future research directions. METHODS: To identify pertinent articles for this review, the MEDLINE database was searched from 1990 to June 2006 using the terms sex, gender, antiretroviral therapy, ART, HAART, pharmacokinetics, pharmacodynamics, NRTI, NNRTI, and protease inhibitors. Search results were restricted to English language and human studies. The reference lists of identified articles were also used, as well as abstracts from relevant conferences. In addition, individual antiretroviral drugs were searched by sex/gender or by pharmacokinetics. RESULTS: Current evidence, though limited, does suggest the existence of a sex disparity in antiretroviral pharmacokinetics, and such disparity has been shown to have pharmacodynamic implications for some drugs. Sex-mediated intracellular pharmaco-enhancement was associated with superior antiviral activities for the zidovudine and lamivudine members of the nucleoside reverse transcriptase inhibitor class. There appears to be divergent opinions about whether sex is a significant determinant of either nevirapine or efavirenz plasma concentrations. For certain protease inhibitors (PIs) (eg, saquinavir [SQV] and indinavir [IDV]), clinically significant relationships between sex differences in plasma drug concentrations and clinical outcomes have been observed. There appears to be a trend toward higher drug exposure in women than in men when PIs are boosted with ritonavir (RTV). Nelfinavir, the only PI that is currently administered unboosted with RTV, does not exhibit a sex difference in its plasma concentrations. Unboosted amprenavir exposure was lower in women compared with men. Sex differences in the pharmacokinetics of SQV and IDV were observed only in the setting of RTV boosting. CONCLUSIONS: A common weakness in many studies addressing sex-based differences in the pharmacokinetics of antiretroviral drugs is the relatively small number of women participating. Many of these studies were retrospective in design, and some had limited pharmacokinetic parameters for comparison. Antiretroviral treatment trials should be designed with sufficient power (adequate female participation) to detect sex-based differences both in pharmacokinetics and in clinical response. Future studies should explore the molecular basis for sex-based differences in plasma drug concentrations and antiretroviral drug response. The roles of drug transporter proteins and cellular kinases, and the activities of metabolizing enzymes in mediating differential plasma and intracellular antiretroviral concentrations, should be further assessed.

Interconception Challenges of Women Who Had Prior Preterm Births.

OBJECTIVE: To describe the interconception challenges of women who had prior preterm births. DESIGN: We used a cross-sectional design and collected data via survey. SETTING: King County, Washington. PARTICIPANTS: Ninety-two women who had prior early preterm births (20-33 weeks gestation) were included. METHODS: Women were recruited from a larger study focused on exploring the infectious pathways for early preterm birth. Participants were interviewed once using open-ended and close-ended surveys. The primary open-ended survey question was What are the five greatest challenges you experience now? We analyzed data using inductive and summative content analysis and descriptive statistics. RESULTS: Ninety-one participants described challenges. One participant had no challenge. We categorized 11 challenges during the interconception period: Mothering (n = 70, 76%), Self-Care Desires (n = 35, 38%), Finances (n = 31, 34%), Employment (n = 31, 34%), Partner Relationships (n = 29, 32%), Individualized Concerns (n = 25, 27%), Mental Health (n = 23, 25%), Balance (n = 22, 24%), Physical Health (n = 19, 21%), Housing (n = 18, 20%), and Family (n = 17, 19%). CONCLUSION: Participants described an array of challenges that often related to their roles as mothers, employees, and partners. Our research advances knowledge by describing contemporary challenges of women during the interconception period.

HIV-1 shedding from the female genital tract is associated with increased Th1 cytokines/chemokines that maintain tissue homeostasis and proportions of CD8+FOXP3+ T cells.

BACKGROUND: HIV-1 shedding from the female genital tract is associated with increased sexual and perinatal transmission and has been broadly evaluated in cross-sectional studies. However, few longitudinal studies have evaluated how the immune microenvironment effects shedding. METHODS: Thirty-nine HIV-1-infected women had blood, cervicovaginal lavage, and biopsies of the uterine cervix taken quarterly for up to 5 years. Cytokines/chemokines were quantified by Luminex assay in cervicovaginal lavage, and cellular phenotypes were characterized using immunohistochemistry in cervical biopsies. Comparisons of cytokine/chemokine concentrations and the percent of tissue staining positive for T cells were compared using generalized estimating equations between non-shedding and shedding visits across all women and within a subgroup of women who intermittently shed HIV-1. RESULTS: Genital HIV-1 shedding was more common when plasma HIV-1 was detected. Cytokines associated with cell growth (interleukin-7), Th1 cells/inflammation (interleukin-12p70), and fractalkine were significantly increased at shedding visits compared with non-shedding visits within intermittent shedders and across all subjects. Within intermittent shedders and across all subjects, FOXP3 T cells were significantly decreased at shedding visits. However, there were significant increases in CD8 cells and proportions of CD8FOXP3 T cells associated with HIV-1 shedding. CONCLUSIONS: Within intermittent HIV-1 shedders, decreases in FOXP3 T cells at the shedding visit suggests that local HIV-1 replication leads to CD4 T-cell depletion, with increases in the proportion of CD8FOXP3 cells. HIV-1-infected cell loss may promote a cytokine milieu that maintains cellular homeostasis and increases immune suppressor cells in response to HIV-1 replication in the cervical tissues.

Generation C: prevalence of and risk factors for chlamydia trachomatis among adolescents and young women in Lima, Peru.

OBJECTIVE: Adolescent and young adult women in urban, socioeconomically disadvantaged areas are at high risk of contracting sexually transmitted infections (STIs). We assessed associations of Chlamydia trachomatis (CT) infection with both traditional STI risk factors, and partner and partnership-related factors among low-income women in Lima, Peru, by age group. METHODS: In a cross-sectional analysis of CT infection among 1290 postpartum women, cervical swabs were collected for CT polymerase chain reaction (PCR) within 48 h after delivery, and a structured interview was completed. Multivariate logistic regression was used to evaluate risk factors for CT, with separate models stratified by age: adolescents (12-19 years), young women (20-24 years), and older women (>or=25 years). RESULTS: CT was detected in 9.6% of adolescents, 9.0% of young women, and 5.4% of older women (p = 0.03). Among adolescents, history of drug use (odds ratio [OR] = 5.62, 95% confidence interval [CI] 1.03-30.6) and short duration of current partnership (OR = 2.6, 95% CI 1.14-5.93) were the strongest predictors of CT infection. Among young women, younger age at coitarche (OR = 0.74 for each year older, 95% CI 0.60-0.91) and low income (OR = 2.40, 95% CI 1.04-5.55) were associated with CT, while self-report of ever using condoms was protective (OR = 0.22, 95% CI 0.08-0.61). Among older women, only younger age at coitarche was related to CT (OR = 0.85, 95% CI 0.75-0.97). CONCLUSIONS: Risk factors for CT among women in Lima, Peru, differed for adolescents, young women, and older women, which may reflect differences in biology and/or immunology of CT as well as variability in the occurrence of specific risk behaviors by age group.

Bacterial vaginosis, not HIV, is primarily responsible for increased vaginal concentrations of proinflammatory cytokines.

The relative effect of HIV-1 infection compared with vaginal infections on vaginal cytokine concentrations is not well characterized. We compared vaginal fluid samples from HIV-1-infected women with those from HIV-negative women, to assess the effect of HIV-1 infection on concentrations of vaginal proinflammatory cytokines and the mucosal defense molecule secretory leukocyte protease inhibitor (SLPI). Twenty-seven HIV-1-infected women and 54 HIV-negative controls, matched for bacterial vaginosis (BV) status, had proinflammatory cytokine [interleukin (IL)-1beta, IL-6, IL-8] and SLPI concentrations measured from archived cervicovaginal lavage and vaginal swab samples using an enzyme-linked immunosorbent assay (ELISA). Log-transformed concentrations were compared by BV and HIV status in univariate analysis using Student's t-test, and in multivariate analysis using a linear regression model. In univariate analysis there were no significant differences in cytokine concentrations among HIV-1-infected and HIV-negative women. In a multivariable linear regression model, BV was significantly associated with an increase in IL-1 beta (p = 0.003). HIV infection was associated with an increased concentration of SLPI (p = 0.008), while BV status was significantly associated with a decrease in SLPI concentrations (p = 0.005). Neither HIV nor BV was associated with changes in IL-6 or IL-8. HIV does not have a major impact on vaginal concentrations of proinflammatory cytokines when controlling for the presence of bacterial vaginosis.